Merck’s Chief Medical Officer’s Thoughts on Eli Lilly’s GLP-1 Approach
GLP-1 has been the biopharmaceutical blockbuster of the past few years, and these effective weight loss drugs will forever be a watershed moment in the long battle against obesity. Not for religious reasons, but from a calendar perspective, the era before GLP-1 was probably like BC. Yes, there are questions about whether people can maintain weight loss after stopping the medication, but the rapid weight loss and accompanying heart benefits are real.
However, if you think the story begins and ends with their impact on weight loss and their evolution from injectables to orals, think again. If Eli Lilly's CEO and Merck executives are to be believed, this is a class of drugs that could become a platform technology that can be applied to a variety of diseases. Indeed, speaking on a BCG (Boston Consulting Group) panel during JPMorgan Week on Tuesday, Merck's chief medical officer painted a picture of how the approach is evolving, driven in large part by the accelerated pace of innovation.
“One of the things that's different today is that innovation goes beyond traditional therapeutic area designations. So you have a lot of biological, inflammatory, fibrotic, degenerative diseases that may have very, very similar pathways,” noted Eliav Barr, who is also Merck's senior vice president and head of global clinical development. “So we're interested in drugs that enable a multifaceted approach. For example, you might have a drug that's important for a disease like atherosclerotic cardiovascular disease or joint disease or Parkinson's disease or HFpEF, a common type of heart failure, and it might be related to inflammation. So this is actually a very powerful way to leverage our discoveries and business development and think about how to maximize the ability to impact the underlying biological mechanisms to help patients in a very broad range of diseases.”
Barr then gave a clear example of the approach being taken by Eli Lilly, the Indianapolis-based drugmaker best known for its popular Zepbound GLP-1 drug.
“As an example, I should say, look at how Eli Lilly combined classic rheumatology drugs or autoimmune disease drugs, and their GLP-1 showed that not only could you improve weight, but you could also improve joint symptoms,” Barr explained. “So I think this TOGETHER study is very smart and is the wave of the future, where you might be able to address multiple diseases within a given therapeutic cluster. So it's not like, 'Oh, I'm really interested in kidney disease.'” Here's more [like]”I'm interested in inflammation. I'm interested in things like fibrosis.”
Earlier this week, at an event hosted by Nvidia, Eli Lilly and Company CEO David Ricks laid out the idea of moving GLP-1 beyond direct therapeutic areas such as obesity and weight loss. Nvidia has become an integral part of the life sciences industry.
“We know you've lost weight. Taking our Zepbound today, you've lost an average of 23 percent of your weight. But we're starting to see a bunch of obvious things, like a reduction in heart attacks and improvements in other metabolic systems in diabetes, prediabetes. The conversion rate to diabetes is down 93 percent,” Ricks declared.
In addition to heart disease and prediabetes, there are positive effects on the comorbidities of being overweight, which Ricks classifies as “non-obvious” use cases for GLP-1. Foremost among these is the issue of inflammation.
“So obesity can cause excessive inflammation, not as acutely in response to an event, but chronically. And that's bad for you. It's bad for your cardiovascular system. It's bad for your joints. So, in our early trials, people would spontaneously report, 'I just lost weight, but I can actually stand up from a sitting position for the first time in 10 years.' Or some people with Crohn's disease and colitis reported some degree of relief from their symptoms.”
Referring to the TOGETHER-PsA open-label phase 3b trial, which tested Eli Lilly's psoriatic arthritis drug Taltz (ixekizumab) and Zepbound (tirzepatide) alone against Taltz, Ricks said the combination increased Taltz's efficacy by 50%. Earlier this month, Eli Lilly reported that 31.7% of patients in the Taltz plus Zepbound arm of the study experienced a 50% improvement in PsA activity and weight loss of at least 10%, compared with 0.8% of patients in the Taltz monotherapy arm.
This is a jaw-dropping result, with more results to be announced in the first half of this year.
Not all companies have GLP-1, but broadly speaking, its impact on overall drug development in the biopharmaceutical space seems clear: a disease-specific platform approach rather than a single therapy for a single disease may be the next evolution in drug development.
Photo: Tara Moore, Getty Images
